RNA-Binding Proteins as Novel Oncoproteins and Tumor Suppressors in Breast Cancer
Abstract
The level of an mRNA depends not only on its rates of synthesis, processing, and transport, but also its rate of turnover. This is particularly important for oncoproteins and cell cycle proteins because their sustained synthesis can favor cell growth rather than differentiation, a hallmark of the neoplastic phenotype. This control is exerted via a balance between the action of at least two RNA-binding proteins, AUF1 and HuR. AUF1 targets the degradation of mRNA like the c-myc proto-oncogene and the cell cycle regulator cyclin D1. By contrast, HuR promotes stabilization of mRNAs. C-myc and cyclin D1 are particularly important in this regard, since both can play a causative role in mammary tumorigenesis. In Phase I, we are examining the effects of AUF1 and HuR expression levels on gene expression in cultured cells. In Phase II, we will assess the roles of AUF1 and HuR in cell growth and tumorigenesis in vivo. During this funding period, we have initiated work on Phase I by creating the expression vectors that will permit either overexpression or knocked-down expression of AUF1 or HuR (e.g. low, medium, or high expression levels) in human breast carcinoma cells. Selection of stably transfected cells has also begun.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA436941
Entities
People
- Gary Brewer